Segregation at three loci explains familial and population risk in Hirschsprung disease

Hirschsprung disease (HSCR), the most common hereditary cause of intestinal obstruction, shows considerable variation and complex inheritance. Coding sequence mutations in RET, GDNF, EDNRB, EDN3 and SOX10 lead to long-segment (L-HSCR) and syndromic HSCR but fail to explain the transmission of the much more common short-segment form (S-HSCR). We conducted a genome scan in families with S-HSCR and identified susceptibility loci at 3p21, 10q11 and 19q12 that seem to be necessary and sufficient to explain recurrence risk and population incidence. The gene at 10q11 is probably RET, supporting its crucial role in all forms of HSCR; however, coding sequence mutations are present in only 40% of linked families, suggesting the importance of noncoding variation. Here we show oligogenic inheritance of S-HSCR, the 3p21 and 19q12 loci as RET-dependent modifiers, and a parent-of-origin effect at RET. This study demonstrates by a complete genetic dissection why the inheritance pattern of S-HSCR is nonmendelian.     

The use of nuclear emulsions to determine small amounts of P33 present in samples of P32

Zusammenfassung Es wird eine Methode beschrieben, welche die Bestimmung kleiner Mengen P³³ in altem Radiophosphor erlaubt: P³³-Beta-Spuren werden ausgezählt in 200 dicken Emulsionsschichten, in denen sie in ihrer ganzen Reichweite enthalten sind.     

The Jurassic-Cretaceous transition of Southern Sweden—palynological and sedimentological interpretation

Palynological studies on the Vitab?ck Clay help resolve the position of the Jurassic-Cretaceous boundary in southern Sweden. Well-preserved assemblages of terrestrial pollen and spores, together with abundant algae (Botryococcus), and for the first time, dinoflagellates have been identified in the Vitab?ck Clay. A Berriasian age is corroborated for the Vitab?ck Clay based on the palynological data; the Jurassic-Cretaceous boundary being placed around the contact of this unit with the underlying “Nytorp Sand”. The terrestrial vegetation was dominated by coniferous forest with an understorey of ferns in a warm, temperate climate. The palynoflora shows compositional similarities to the Northern Chinese Floral Province and especially the Jehol Group. The majority of the Vitab?ck Clay represents a moderate-to low-energy paralic succession. However, the basal part of the unit incorporates anomalously coarse material of mixed terrestrial and marine origin. This sedimentary package is herein interpreted to represent tsunami deposits and is similar to coeval tsunami-related deposits in France.     

Placental and fetal contraindications of dexamethasone administration to pregnant rats

Summary Dexamethasone (DEXA) given to pregnant rats for either the last 3 or 6 days of gestation lowered placental, fetal body and adrenal weights. Histologically, DEXA-treated placentas appeared smaller than controls and showed signs of necrosis and pyknosis. Treated animals that were permitted to carry their litters to term did not deliver naturally, and most of their fetuses were dead when excised 1 day postmaturely.     

Mutagenic insertion and chromosome engineering resource (MICER)

Embryonic stem cell technology revolutionized biology by providing a means to assess mammalian gene function in vivo. Although it is now routine to generate mice from embryonic stem cells, one of the principal methods used to create mutations, gene targeting, is a cumbersome process. Here we describe the indexing of 93,960 ready-made insertional targeting vectors from two libraries. 5,925 of these vectors can be used directly to inactivate genes with an average targeting efficiency of 28%. Combinations of vectors from the two libraries can be used to disrupt both alleles of a gene or engineer larger genomic changes such as deletions, duplications, translocations or inversions. These indexed vectors constitute a public resource (Mutagenic Insertion and Chromosome Engineering Resource; MICER) for high-throughput, targeted manipulation of the mouse genome.     

Genome sequence of Silicibacter pomeroyi reveals adaptations to the marine environment

Since the recognition of prokaryotes as essential components of the oceanic food web, bacterioplankton have been acknowledged as catalysts of most major biogeochemical processes in the sea. Studying heterotrophic bacterioplankton has been challenging, however, as most major clades have never been cultured or have only been grown to low densities in sea water. Here we describe the genome sequence of Silicibacter pomeroyi, a member of the marine Roseobacter clade (Fig. 1), the relatives of which comprise approximately 10-20% of coastal and oceanic mixed-layer bacterioplankton. This first genome sequence from any major heterotrophic clade consists of a chromosome (4,109,442 base pairs) and megaplasmid (491,611 base pairs). Genome analysis indicates that this organism relies upon a lithoheterotrophic strategy that uses inorganic compounds (carbon monoxide and sulphide) to supplement heterotrophy. Silicibacter pomeroyi also has genes advantageous for associations with plankton and suspended particles, including genes for uptake of algal-derived compounds, use of metabolites from reducing microzones, rapid growth and cell-density-dependent regulation. This bacterium has a physiology distinct from that of marine oligotrophs, adding a new strategy to the recognized repertoire for coping with a nutrient-poor ocean.     

Quality assessment of the human genome sequence

As the final sequencing of the human genome has now been completed, we present the results of the largest examination of the quality of the finished DNA sequence. The completed study covers the major contributing sequencing centres and is based on a rigorous combination of laboratory experiments and computational analysis.